1. Field of the Invention
The present invention relates generally to copper salts of ion exchange materials that provide copper ions at levels suitable for use as an anti-infective agent. In certain aspects of the invention, copper salts of cellulose derivatives are provided. The copper salts of ion exchange materials may be formed using ether and ester derivatives of cellulose, such as carboxymethyl cellulose (CMC), ethylcellulose (EC), methylcellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), hydroxyethyl methyl cellulose (HEMC), cellulose acetate, and cellulose triacetate. The present invention also relates to wound dressings having copper salts of ion exchange materials incorporated therein. The copper salts of ion exchange materials may produce an equilibrium of copper ions in a wound at a level that is therapeutically-effective for preventing infection. Wound dressings containing copper salts of ion exchange materials may be used in accordance with methods of reducing the incidence of infection in wounds such as lacerations, abrasions, and burns. The wound dressings may also be used in accordance with methods for preventing infections in long-term wounds, such as those formed at wound drain, catheter, and ostomy entry sites. In further aspects of the invention, copper salts of ion exchange materials may be used to carry out methods of killing microorganisms, and may optionally be used in conjunction with additional anti-infective agents.
2. Description of Related Art
Surgical Site Infections (SSIs) account for approximately 500,000 nosocomial infections each year an added cost of more than $3,000 per infection, with a total impact on the healthcare system being over $1.5 billion per year. The post operative infection rates for surgical procedures averages between 2% to 4% for all procedures with selected procedures having significantly higher rates. The surgical procedures associated with the highest rates of infection and morbidity include coronary artery bypass graft (CABG), cardiac surgery, colon surgery, hip arthroplasty, knee arthroplasty, hysterectomy, thromboendarterectomy, and vein bypass.
In addition, approximately 30% of patients undergoing hemodialysis have permanent central line catheters (CLSs), and these patients experience insertion site and bloodstream infections (BSIs) at high rates. Other indwelling catheters are also associated with high rates of infection.
A number of approaches have been developed in an attempt to address the problem of infections in wounds, such as wounds formed by surgical procedures, lacerations, abrasions, burns, as well as long-term or chronic wounds such as those formed at wound drain sites, catheter entry sites, and ostomy exit sites. Anti-infective agents, including antimicrobial agents, antibiotics, antifungals, and antivirals, have been incorporated into a variety of wound care products such as wound dressings, bandages, creams, and ointments.
Several metals are known to possess antimicrobial properties, including silver, copper, lead, cadmium, palladium, and zinc. Of these, copper has the advantage of being a naturally-occurring ion found in the human body. Copper is found in human plasma in concentrations of about 0.85 ug/ml+/−0.19, and its presence in the body is known to be tolerated for long periods of time, as evidenced by the use of medical devices such as the copper-coated IUD.
UK Patent Application No. GB 2 092 006 describes a germicidal wound or burn dressing including an absorbent pad and a non-absorbent liquid-permeable sheet that is coated with metallic copper or a copper compound. The copper-containing sheet is placed in contact with the wound or burn, and protects against bacteria without causing the bacteria to develop resistance.
U.S. Pat. No. 4,637,820 describes a modified fibrous material comprising cellulose fibers that are substituted at their cellulose anhydroglucose units with anionic moieties, and capped by copper cations such that the fibers bind from about 0.1% by weight to about 3.0% by weight of copper based on the weight of the fibers. Methods of preparing a copper-modified carboxyalkyl cellulose fiber are also described, which include treating the fibers with an aqueous cupric salt solution and washing the fibers to remove the salt, followed by drying. The fibers preferably have a degree of copper substitution of from 0.01 to 0.3. Materials prepared using the fibers may include surgical dressings, absorbent cotton, and various hygienic devices.
U.S. Pat. No. 5,977,428 describes absorbent dressings for absorbing exudates from wounds, where the dressings contain a plurality of absorbent hydrogel particles sealed within a porous container. The porous container does not adhere to the wound, and the hydrogel particles remain sealed in the container after absorbing the exudate. The particles may be dried polyacrylonitrile hydrogel particles, and the particles may contain or release wound healing agents or nutrients that aid the healing process, such as copper- and zinc-containing compounds or complexes.
PCT Published Application No. WO 2008/101417 describes a hydrogel dressing for covering or treating a wound, and methods for preparing such dressings. The dressing includes a matrix structure including a cross-linked mixture, and an elastic sheet coated with an elemental metal or an ionic metal that is embedded in the matrix structure. The cross-linked mixture comprises a hydrophilic polymer, a photocatalyst, and water. The metal is preferably. TiO2 in combination with silver ions, although zinc and copper may also be used in place of the silver.
U.S. Published Application No. 2008/0311165 describes methods for treating and healing sores, cold sores, cutaneous openings, ulcers, lesions, abrasions, burns, and skin conditions by applying a polyamide, polyester, acrylic, or polyalkylene material having water-insoluble copper oxides embedded therein. The material releases copper (I) ions, copper (II) ions, or combinations thereof upon contact with a fluid.
Current anti-infective dressings available on the market incorporate silver as an anti-infective agent. These dressings are expensive (about 5-10 times more expensive than conventional dressings), and are therefore are only used for severe burns, chronic non-healing wounds, and in high-risk patients. Exemplary dressings include Argentum Medical's SilverIon® dressing, Johnson & Johnson's Acticote® dressing, Medline's Argalase® dressing, Smith & Nephew's Actisorb® dressing, and Conoplast's Contreed® dressing. Although there are a variety of silver-based products available on the market, the high prices associated with these dressings deters their use in many situations where they might be helpful in preventing infections. Further, although silver and other metals such as lead, palladium, cadmium, and zinc can be effective as antimicrobial agents, these metals can accumulate in the body and are not easily eliminated, which can be detrimental to the healing process.
There is a need in the art for cost-effective anti-infective products. There is also a need for articles of manufacture that provide anti-infective properties by releasing copper ions in a controlled, consistent manner when contacted with fluids, such as water, perspiration, and wound exudates. Such articles may incorporate copper salts of ion exchange resins, where the articles may be in the form of, e.g., wound dressings, gauzes, bandages, and/or topical preparations in the form of creams, gels, hydrogels, and ointments. The articles that release copper ions may produce an equilibrium of copper ions in a wound at a level that is therapeutically-effective for preventing infection. Further, the anti-infective products in accordance with the present invention provide a cost-effective alternative to currently-available silver-based anti-infective dressings, thereby broadening the number of applications for which the anti-infective dressings of the present invention may be used.